1h-3-(substituted aminoalkylidene) cyclopenta {8 {62 {9 {0 thianaphthenes

ABSTRACT

The compounds are 1H-3-(substituted aminoalkylidene)cylclopenta( Beta ) thianaphthenes which are useful as central nervous stimulants of the antidepressant type and anticholinergic agents. A compound disclosed is 1H-3-( gamma dimethylaminopropylidene)cyclopenta( Beta )thianaphthene hydrochloride.

United States Patent Suh 15] 3,682,967 [4 1 Aug. 8, 1972 54 1H-3-(SUBSTITUTED AMINOALKYLIDENE) CYCLOPENTA THIANAPHTHENES [72] Inventor: John T. Suh, Mequon, Wis.

[73] Assignee: Colgate-Palmolive Company, New

York, N.Y.

[22] Filed: Feb. 9, 1970 [21] Appl. No.: 9,947

Related US. Application Data [63] Continuation-in-part of Ser. No. 599,744, Dec.

7, 1966, Pat. No. 3,497,528.

[52] US. Cl ..260/330.5, 260/240 R, 260/247.1, 260/268 TR, 260/293.57, 260/3265 SA, 260/326.82, 424/248, 424/250, 424/267,

[51] Int. Cl. ..A6lk 27/00, C07d 63/22 [58] Field of Search ..260/330.5

[56] References Cited UNITED STATES PATENTS 3,492,294 1/1970 Suh ..260/240 3,497,528 2/1970 Suh ..260/330.5

Primary Examiner-Henry R. Jiles Assistant Examiner-Cecilia M. Shurko Attorney-T. F. Kryshak and M. L. Youngs [57] ABSTRACT 6 Claims, No Drawings lH-3-(SUBSTITUTED AMINOALKYLIDENE) CYCIJOPENT [B] TIHANAPHTHENFS RELATED CASES This application is a continuation-in-part of my copending application Ser. No. 599,744 filed Dec. 7, 1966, titled 3-Arninoalkyl and 3-Amino Derivatives of Cyclopenta[B]Thianaphthene now US. Pat. No. 3,497,528.

DESCRIPTION'OF INVENTION The compounds of the present invention have the following formula wherein X and Y are hydrogen, halogen such as chloro, bromo or fluoro, hydroxy, nitro, lower alkyl such as methyl, ethyl, propyl or isopropyl, lower alkoxy such as methoxy, ethoxy or propoxy and trifluoromethyl, Z is ()l' Am R1 R is hydrogen or hydroxy, R is hydrogen, a lower alkyl of one to four carbon atoms, or an aralkyl of seven to l 1 carbon atoms such as benzyl, phenethyl and phenylisopropyl, R is R or -CH --B'-Am, B is an alkylene of one to five and- Am is in which R and R may be hydrogen, lower alkyl of one to eight carbon atoms, hydroxy-lower alkyl, an alkoxy alkyl, an alkenyl of three to six carbons such as allyl, 3- butenyl or S-hexenyl, an aryl such as phenyl and nuclear substituted phenyl, an aralkyl of seven to 11 60 carbon atoms, particularly phenyl-lower alkyl such as benzyl, phenyl-ethyl, phenyl-isopropyl and phenyl-butyl, a cycloalkyl of three to seven carbon atoms such as cyclohexyl, a cycloalkyl-lower alkyl in which the cycloalkyl has three to seven carbon atoms such as cyclohexyl methyl and groups in which R, and R are joined together to form amino groups in which the nitrogen is part of a cyclic group such as morpholino, pyrrolidino, pipeyidino, such as N-methylpiperizine, N- phenyl-lower alkyl piperazino or N-hydroxy-lower alkyl piperazino, or Am is is a cyclic amine group, including such groups as N- lower alkyl-2,3 or 4-piperidyls such as N-methyl-3- piperidyl, N-ethyl-4-piperidyl, N-ethyl-2-pipen'dyl and N-isopropyl-3-piperidyl, N-(di-lower alkyl amino-lower alkyl)-2,3 or 4-piperidyls such as N-(betadimethylamino-propyl)-4-piperidyl, N-(betadiethylaminoethyl)-3-piperidyl and N-(betadimethylaminopropyl)-2-piperidyl, N-phenyl-lower alkyl-3 or 4-piperidyls such as N-benzyl-3-piperidyl, N- phenyl-ethyl-4-piperidyl and N-phenylpropyl-3- piperidyl, Z-piperidyl, 3-piperidyl and 4-piperidyl, 2- pyrrolidyl, 3-pyrrolidyl, N-lower alkyl-2 or 3-pyrrolidyls such as N-methyl-2-pyrrolidyl, N-ethyl-B-pyrrolidyl, N-propyl-4pyrrolidyl, and N-phenyl-lower alkyl-2 or 4-pyrrolidyls such as N-benzyl-Z-pyrrolidyl and N-phenyl-ethyl-3-pyrrolidyl and D is COOH, CO R or CN.

The compounds of the present invention may be conveniently prepared by employing as the starting material a lH-cyclopenta [B]thianaphthene-3-one of the formula The ketones may be conveniently prepared as described in the literature (MP. Cagniant and M'" P.

Cagniant: Bulletin de la Societe Chimique de France,

, I 3,682,967 1 3 v 4 X 1H-6-chloro-3-(B-aminoethylidene)-cyclopenta[ v B]thianaphthene,

l H-5-methoxy-3-(,B-aminoethylidene )cyclopent a[ ,Blthianaphthene, Y 5 lH-7-trifluoromethyl-3-(B-aminoethylidene)- cyclopenta-[B]thianaphthene, B l H-6-bromo-3-(B-aminoethylidene )-cyclopenta[ Am B]t hianaphthene. in which R is hydroxy. or hydrogen and B is 10 ilif fifiggg methylene may be readily prepared by treating the starting ketone first with t-butyl acetate and i jfii gi sfg g i diethylamino magnesium bromide to form the coranaphthene y y responding ester, followed by treatment with lithium I aluminum hydride to form the corresponding alcohol, I '1H'6'bmmo'3'm ammoethyl) cyclopemam 1th] hthene and which in turn 18 treated with tosyl chloride and a sultaanapble amine such as disubstituted amine under conven- 1Hlmfluommethyl'3'(B-mmnoethyl) cyclopema' tional conditions to form the compounds in which R is ggi fi gz l h invention which have the hydroxy, which, if desired, can be reduced to form the lowin f compounds in which R is hydrogen or dehydrated to 20 g form the corresponding olefin. X

The above described process may be illustrated as follows:

OH3COOC(0H3)3 S X X R CH2 NMgBr l B Et A Y s s in which R is hydroxy orhydrogen and B is anal- O H0 H2 kylene of one to five carbon atoms may becon- 5)= venie'ntly prepared by treating the starting ketone with a suitable Grignard reagent or organo lithium compound in a suitable inert nonaqueous solvent such as tetrahydrofuran, etc. The resulting alcohol can then be (1) tosylchlorldo hydride or with tosylchloride followed by lithium aluminum hydride to form the compounds in which R is hydrogen.

* The above described process may be diagrammed as 40 follows:

( 1) tosylchlqyido xX X z I I Grignnrd l I N 5 U S Y Y R4 l Ho 1 12 Dehydration l (2) LAH H Am X X A101:

fiififilido I l X X YX/\S Y S LAII H H H, I H 41H; /\5 I I l 11 in Y TSO H2 I l 7 11s 11 R4 R4 I Am A I wherein R and R are other than hydrogen and X Representative of the Grignard reagents and organo and Y represent groups that do not partake in or interlithium compounds vwhich can be employed in this fere with the reactions. process are the following:

Representative of the compounds which may be 5 I dimethylaminopropyl magnesium chloride, prepared by thedescribed process are the following: diethylaminopropyl magnesium bromide,

lH-S-(B-aminoethylidene)-cyclopenta[B]thi- 4-picolyl lithium,

- anaphthene, v l-methyl-4piperidyl magnesium bromide,

treated with aluminum chloride and lithium aluminum Grignard reagents which may be produced by the conventional processes such as those disclosed in US. Pat. No. 2,996,503.

The reaction between the disubstituted aminoalkyl metal halides and the lH-cyclopenta[/3]thianaphthene- 3-0ne is conveniently effected by bringing the reactants together under the conditions generally used for reacting a Grignard reagent with a ketone to form a tertiary alcohol. The reactants are advisably combined in an anhydrous medium such as ethyl ether, tetrahydrofuran, or ethyl ether with benzene. After the reactants have been brought together the mixture can be heated, preferably at reflux, to promote the reaction. When the 2 reaction is terminated water may be added to hydrolyze the Grignard adduct to the desired tertiary alcohol. The resulting product may then be isolated from the mixture by conventional means such as by evaporating the solvent. The product may then be recrystallized from a suitable medium, such as benzene, if desired. The same conditions may be used when an organo lithium compound is employed in the reaction.

Illustrative of the lH-3-(disubstituted aminoalkyl)- cyclopenta[ B]thianaphth er 1e-3;ol which may be produced by the descfibed process are the following:

1 H-3-( y-dimethylaminopropyl )cyclopenta[is1thianaphthene-3-ol,

l H-3-(B-diethylaminoethyl)cyclopenta[ ]thi anaphthene-3-ol, 40

l H-3-(y-piperidinopropyl)cyclopenta[ plthianaphthene-3-ol,

l H-3-(y-N-methyl-N-benzylaminopropyl )cyclopenJ ta[ ]thianaphthene-3-ol,

1 l-l-3-(,B-pyrrolidinoethyl)cyclopenta[B]thianaphthene-3-ol,

l H-3-(y-dicyclohexylaminopropyl )cyclopenta[ B ]thianaphthene-Ii-ol, v

anaphthene-3-ol,

lH-S -chloro-3 -('y-dimethylaminopropyl)cyclopenta llthiawl thsysfizd l H-6-benzyloxy-3-(ydimethylaminopropyl)cyclopentaigflthianaphthene-3-ol, and

1 H-5-trifluoromethyl-3-(y-N-methylpiperazinopropyl)cyclopenta[B]thianaphthene-3- o].

Representative of the compounds which may be obtained by treating the corresponding 3-ols with lithium aluminum hydride and aluminum chloride or altematively, with tosylchloride followed by treatment with lithium aluminum chloride are the following:

1 H-3-(y-dimethylaminopropyl )cyclopenta[is1thianaphthene,

l H-3-(B-diethylaminoethyl )cyclopenta[ ]thianaphthene,

lH-3-(y-dibenzylaminopropyl)cyclopenta[is]thianaphthene, g

1 H- 3-( 'y-N-methyl-N-benzylaminopropyl )cyclopenJ ta[]thianaphthene,

lH-3-(y-piperidinopropyl)cyclopenta[filthianaphthene, v l

lH-B-(B-pyrrolidinoethyl)cyclopenta[B]thi- 4 anaphthene, I

lH-3-(y-dicyclohexylaminopropyl)cyclopenta[B ]thianaphthene, 1

l H-5-chloro-3-(y-dimethylaminopropyl)cyclopenta llth aaa bt p t lH-6-benzyloxy-3-[4'-(N-methyl)piperidyl]cyclop enta[B]thianaphthene, and

l H-S-hydroxy-3-(B-diethylaminoethyl)cyclopenta[ ,B]thianaphthene.

The compounds in which Am is and R5 is hydrogen and R is not hydrogen may be conveniently prepared by subjecting the corresponding compound in which & is benzyl and R is not hydrogen or benzyl to catalytic cleavage of the benzyl group.

Similarly, the compounds in which Am is NH may be prepared by subjecting the corresponding compound in which both R, and R are benzyl to catalytic cleavage of the'benzyl groups.

The catalytic cleavage of the benzyl group may be readily effected by dissolving the N-mono or dibenzyl derivative in a suitable medium and adding a catalyst, such as palladium on carbon, and hydrogen under pressure, as up to about psi.

The cleavage may also be eflected by reacting the appropriate benzyl derivative with a chloroformate such as methyl chloroformate, ethyl chloroformate or the like, to form the corresponding N-carboalkoxy derivative, and subjecting that compound to hydrolysis conditions.

Representative" of the compounds which may be prepared in the described manner are the following: 1 H-3-(y-methylaminopropyl )cyclopenta[ ]thianaphthene, ll-l-3-(-y-ethylaminopropyl)cyclopenta[fi]thianaphthene, lH-3-(B-methylaminoethyl)cyclopenta[B1thianaphthene, lH-B-(B-ethylaminoethyl)cyclopenta[filthianaphthene, 1 H-3-( 'y-aminopropyl )cyclopenta[fihhianaphthene, lH-3-(B-aminopropyl)cyclopenta[B]thianaphthene, 1 H-S-fl uoro-3-( y-aminopropyl )cyclopenta[ B] thianaphthene, and lH-6-trifluoromethyl-3-(B-aminoethyl)cyclopenta[ ,Blthianaphthene. The compound of the formula 3,682,967 7 n V s in which R is hydrogen are readily formed by coni verting the starting ketone to the corresponding oxime H 0 and then treating the oxime with lithium aluminum Y R NI'I Y R (Elia them with hydroxylamine, advisably in an organic reaction medium in which the reactants are soluble. The hydroxylamine can be produced in situ by the neutralization of a hydroxylamine salt such as the hydrochloride. Inorganic bases such as alkali metal 10 v hydroxides, carbonates'and bicarbonates, as well as or- I I hydride to form the primary amine.

The ketones are converted to the oximes by reacting 5 1 ganic bases such as pyridine, can be used to neutralize i f the acid released from the hydroxylamine salt. Am

The described process for preparing the primary X amines may be diagrammed as follows: I

or interfere with the reactions.

The guanidino derivative may be readily prepared by treating a primary amine with methyl pseudothiourea in 70 percent aqueous ethanol under reflux conditions.

The described process may be illustrated as follows:

, LAH

X X R N I NHZOH 20 I v HsEHa in which X is a reactive halide and R is not s s hydrogen, and all other symbols are as previously Y Y defined and represent groups which do not partake in X SCH:

Representative of the compounds which may be I prepared in the above described manner are the following:

1 H-3-aminocyclopenta[ fi]thianaphthene,

1 H-3-amino-5-chlorocyclopenta[B]thianaphthene,

l H-3-amino-5-hydroxycyclopenta[fi]thianaphthene,

and l H-3-amino 6-bromocyclopentaLB]thianaphthene. A wide variety of amine derivatives may be prepared in which all-symbols are as previously defined and represent groups that do notpartake in or interfere with the reaction. v

Representative of the compounds which may be prepared by the above described processes are the following:

1H-3-dimethylarninocyclopentam]thianaphthene,

from the above described primary'amines by conventional techniques. For example, the compounds in which R and/or R are alkyl or aralkyl may be preparedby treating the primary amine with an alkyl halide, and the compounds in which R is CH -B4- 1 H-3-guanidinocyclopenta[ [3]thianaphthene,

lH-3-( 'y-dimethylaminopropylamino )-cyclopenta[ B ]thianaphthene, and

l H-3-methylaminocyclopenta[ B] thianaphthene.

The compounds in which Am is andR is hydrogen or R and R are hydrogen may be prepared by subjecting the corresponding compounds inwhich R, and/or R are benzyl to cleavage of the benzyl groups as was previously described.

s s Y Y R NH: it In I Representative of the compounds which can be prepared in the described manner are the following:

1 H-3-( y-methylaminopropylamino )-cyclopenta[ B ]thia-naphthene, and l H-3-aminopropylaminocyclopenta[B]thiana phthene. The compounds of the invention which have the following formula I X X Cl Grlgnard I S S Y Y (1) Grlgnard (2) Dehydration Am Dehydration IH B as I Am Representative of the compounds which may be obtained by the described process are the following:

lH-3-('y-dimethylaminopropylidene)-cyclopenta[B ]thianaphthene,

l H-3-(B-diethylaminopropylidene)-cyclopenta[B ]thianaphthene,

l H-3-('y-N-methyl-N-benzylaminopropylidene cyclpenta[B]thianaphthene,

lH-3-(fi-pyrrolidinopropylidene)-cyclopenta[B]thianaphthene,

l l-l-3-('y-dicyclohexylaminopropylidene )-cyclopenta[/3]thianaphthene,

lH-3-(y-4-methylpiperazinopropylidene)-cyclopen- 5 ta[B]thianaphthene, 1I-l-5-chloro-3-[4-(N-methyl)piperidylene]cyc lopenta[fi]thianaphthene, and

methyl)piperidylene]cyclopenta[/3]thianaphthene, and a l H-S-meth0xy-3-(y-dimethylaminopropylidene )cyclopenta [B]thianaphthene.

The compounds in which B is methylene may be prepared as described previously or by treating the 0 ketone starting material with triethylphosphononitrile to form the corresponding methylene nitrile derivative and then reducing the nitrile with an agent such as lithium aluminum hydride to form the primary amine which, of course, may be converted by conventional means into a wide variety of secondary and tertiary amines.

This process may be illustrated as follows:

W T e 5 S Y Y H 6H2 kHz The novel compounds of the formula in which D is CO R may be prepared by treating the ketone starting material with triethylphosphonoacetate to form the ethyl ester, hydrolyzing the ethyl ester by treating it with an alkali hydroxide to form the free acid. If desired, the free acid may be then treated with a secondary amine such as dimethylamine to form the amide which upon treatment with lithium aluminum hydride yields the substituted amine. The compounds in which D is CO R, thus serve as convenient intermediates for the preparation of the corresponding arrunes.

The processes may be illustrated as follows:

CH; KOH 1 HN x CH: X

2 LAH s a s Y I Y n H on $0.11

Representative of the compounds which may be prepared by this process are the following:

1 H-3-( carbethoxyrnethylene )cyclopenta[ B] thiana phthene,

lH-3-(carboxymethylene)cyclopenta[fi]thiana phthene,

lH-5-fluoro-3-(carbethoxymethylene)cyclopenta[,8

]thianaphthene,

1 l-l-6-chloro-3-( carboxymethylene )cyclopenta[ hs lthianaphthene,

l l-I--bromo-3-( carboxymethylene )cyclopenta[ hs ]thianaphthene, and 1 11-5 -trifluoro-3-( carbethoxymethylene)cyclopenta [B]thianaphthene.

Acid addition salts of the compounds of the present invention, capable of forming such salts, may be conveniently prepared by contacting the compounds with a suitable acid such as formic acid, citric acid, maleic acid, sulfuric acid, hydrochloric acid, succinic acid, tartaric acid, benzoic acid or fumaric acid.

Quartemary ammonium salts may be formed by contacting the compounds which are capable of forming such salts with a suitable alkylating agent such as dimethyl sulfate or an alkyl halide such as methyl chloride, methyl iodide or ethyl bromide.

The novel compounds of the present invention, which are amines, and their pharmaceutically acceptable salts have utility as central nervous stimulants of the antidepressant type and anticholinergic agents. For example, the compounds lH-3-aminocyclopenta[,8]thianaphthene hydrochloride and 1H-3-(7-dimethylaminopropylidene)cyclopenta[ ]thianaphthene hydrochloride in non-lethal doses of about mg/kg intraperitoneally caused central nervous system stimulation in mice. In addition, the lH-3-(ydimethylaminopropylidene )cyc1openta[B]thianaphthene hydrochloride was found to possess an anticholinergic activity when evaluated in the isolated guinea pig ileum preparation.

The compounds are preferably combined with one or more suitable pharmaceutical diluents and formed into unit dosage forms. Such dosage forms provide suitable means for oral and parenteral administration.

The pharmaceutical diluents which may be em-- ployed may be either liquid or solid, but the preferred liquid carrier is water. In the event the compound is not soluble in water a pharmaceutically acceptable organic solvent such as propylene glycol may be employed.

Solid pharmaceutical diluents such as starch, sugar and talc can be utilized to form powders which can in turn by used as such or may be tableted or encapsulated. In addition to the forementioned material, a wide variety of conventional pharmaceutical lubricants, disintegrating agents, flavoring agents and the like may also be employed.

The unit dosage forms may contain a concentration of 0.1 to 10 percent or more by weight of one or more of the novel compounds. Generally, such dosage forms will contain about 5 to 150 mg. of the active ingredients. One or more of such dosage forms may be administered daily.

The following examples are presented to illustrate this invention:

EXAMPLE] 1 H-Cyclopenta[ ,8] thianaphthene-3-one A solution of 2.7 g. (0.0131 mole) of BBS-thianaphthenyl)-propionic acid in 50 ml. of thionyl chloride is allowed to'reflux for 25 minutes and the excess thionyl chloride is distilled in vacuo. To the residue in 50 ml. of anhydrous benzene is added in portions 3 g. of anhydrous aluminum chloride with cooling and the reaction mixture stirred overnight at room temperature. The reaction mixture is cooled and treated with ice water and 25 ml. of 10 percent hydrochloric acid solution. The organic layer is separated and the aqueous layer extracted with 50 ml. of benzene. The combined benzene solution is washed successively with water, saturated sodium bicarbonate, water, and dried over anhydrous sodium sulfate. The benzene solution is distilled in vacuo and the residue recrystallized from ethanol to give 1l-l-cyclopentaLB]thianaphthene-3-one, m.p. 160-161.

Anal. Calcd. for C H OS; S, 17.03.

Found: 8, 17.07.

' EXAMPLE 2 ll-I-Cyclopenta[,8]thianaphthene-3-one oxime To a solution of 1.3 g. (0.069 mole) of the ketone of Example 1 in ml. of ethanol is added with Stirring a solution of 0.69 g. (0.01 mole) of hydroxylamine hydrochloride in 10 ml. of water and 0.8 g. (0.01 mole) of sodium acetate in 10 ml. of water. The reaction mixture is then allowed to reflux for 10 minutes and stirred overnight at room temperature. The reaction mixture is diluted with 100 ml. of water and the product filtered and recrystallized from dilute ethanol to give the oxime, m.p. 222.

Anal. Calcd. for C l-I NOS: S, 15.78.

Found: S, 16.07. 1

EXAMPLE 3 l H-3-Aminocyclopenta[fl] thianaphthene Hydrochloride To a suspension of 3.68 g. (0.1 mole) of lithium aluminum hydride in ml. of tetrahydrofuran (Tl-1F is added in portions 4.6 g. of the oxime and the mixture allowed to reflux for one hour and then stirred at room temperature for 2 hours. An additional 200 ml. of THF is added and the reaction mixture carefully decomposed with 20 ml. of water. The reaction mixture is filtered and the residue washed with THF. The combined solution is distilled in vacuo and the basic residue converted to the hydrochloride salt in ether.,The salt is dissolved in 200 ml. of water, made basic with 5 percent sodium hydroxide solution, extracted with two 100 m1. portions of ether, and dried over anhydrous sodium sulfate. The basic residue is converted to the hydrochloride salt in ether and recrystallized from methanol-ether to give 1H-3-aminocyclopenta[fi]thianaphthene hydrochloride, light brown powder m.p. 261263.

Anal. Calcd. for C I-I ClNS: C, 58.54; H, 5.36; N,

Found: C, 58.31; H, 5.63; N, 5.96; Cl, 15.35.

EXAMPLE 4 1H-3-('y-Qimethylaminopropyl)cyclopenta[B ]tl'1ianaphthene-,3-o1 Hydrochloride To the Grignard reagent prepared from 219 g. (0.09

mole) of magnesium and 10.9 g. (0.13 mole) of freshly distilled 'y-dimethylaminopropyl chloride in 100 ml. of

' Tl-lF is added in portions a solution 8.5 g. (0.045 mole) of the ketone of Example 1 in 100 ml. of TI-IF over onehalf period. The reaction mixture is stirred at room temperature for 16 hours and decomposed with 20 ml. of saturated ammonium chloride. The reaction mixture is filtered and the residue washed with THF. The combined Tl- F soluu'on is distilled in vacuo and the basic residue dissolved in ether. The ether insoluble material is removed by filtration and the ether solution washed with water, dried over anhydrous sodium sulfate, and treated with anhydrous hydrogen chloride. The product is recrystallized from ethanol-ether to give 1H- 3-( 'y-dimethylaminopropyl )cyclopenta[ is thianaphthene-3-ol hydrochloride, light brown powder, m.p. l85-187.

Anal. Calcd. for C I-I CINOS: Cl,

Found: Cl, 11.09.

EXAMPLE 5 1 H-3-( 'y-Dimethylaminopropylidene )cyclopenta[ B lthianaphthene Hydrochloride To the Grignard reagent prepared from 3.0 g. (0.12 mole) of magnesium and 14.9 g. (0.12 mole) of 'ydimethylaminopropyl chloride in 100 ml. of THF is added a solution of 11.5 g. (0.06 mole) of 1H- cyclopenta[B]thianaphthene-3-one in 200 ml. of THF over 1% hours. The reaction mixture is stirred at room temperature for 16 hours and decomposed with 30 ml. of saturated ammonium chloride solution. The reaction mixture is filtered and the residue washed with THF. The combined THF solution is distilled in vacuo, and the ether solution washed with water, dried, and adjusted to pH 6 slowly with ethereal hydrogen chloride. The product is recrystallized once from ethyl alcohol and once from methyl alcohol and dried in vacuo at 1 10 to yield 1 H-3('y-dimethylaminopropylidene)cyclopenta[/3]thianaphthene hydrochloride, mp. 21 l-2 1 3. After two recrystallizations from ethyl alcohol the product melted at m.p. 2l3-2l4.5.

Anal. Calcd. for C H CINS: C, 65.40; H, 6.86; N,

4.77. Found: C, 64.90; H, 7.00; N, 4.67.

EXAMPLE 6 lH-3-(Carbethoxymethylene)cyclopenta[fl]thiana phthene To a solution of 3.84 g. (0.08 mole) of 50 percent sodium hydride in 250 m1. of freshly distilled dimethoxyethane is added 17.9 g. (0.08 mole of triethylphosphonoacetate dissolved in 30 ml. of

dimethoxyethane within 15 minutes while maintaining the reaction temperature at l5-20. The solution is stirred at room temperature for 1 hour after which 15 g. (0.08 mole) of finely ground lH-cyclopenta[B]thianaphthene-B-one is added in portions within 10 minutes. The mixture is stirred at room temperature for 16 hours and refluxed for 2 hours. The mixture is cooled, poured into 3.5 liters of ice water, and cooled. The resulting solids are collected by filtration, dried, and extracted with 200 ml. of refluxing chloroform the insoluble material is removed by filtration and the filtrate concentrated in vacuo to yield a dark solid which is dissolved in 100 ml. of ethanol. The insoluble material is again removed by filtration and the filtrate cooled tac ihyaiggd a crystalline S0il$ie gich 1s rom ymethylene)cyclopenta[B]thianaphthene in the form of a gold brown crystalline solid, mp. l37l 39.

Anal. Calcd. C ,I-l,.,O S: C, 69.74; H, 5.47.

Found: C, 69.74; H, 5.54.

We claim:

1. A compound selected from the compounds of the formula wherein X and Y are selected from hydrogen, halogen or trifluoromethyl, B is an alkylene of one to five carbon atoms and Am is in which R, and R are selected from hydrogen, lower alkyl of l to 8 carbon atoms and phenyl-lower alkyl and pharmaceutically acceptable salts thereof.

2. A compound of claim 1 in which X and Y are hydrogen.

3. A compound of claim 1 in which B is ethylene.

4. A compound of claim 1 in which B is propylene.

5. A compound of claim 1 in which R and R are selected from hydrogen, methyl, ethyl and benzyl.

6. A compound of claim 1 in which X and Y are hydrogen, B is ethylene and R and R are methyl. 

2. A compound of claim 1 in which X and Y are hydrogen.
 3. A compound of claim 1 in which B is ethylene.
 4. A compound of claim 1 in which B is propylene.
 5. A compound of claim 1 in which R3 and R4 are selected from hydrogen, methyl, ethyl and benzyl.
 6. A compound of claim 1 in which X and Y are hydrogen, B is ethylene and R3 and R4 are methyl. 